Sunday O. Olayemi

The knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria.

Community Pharmacists both have an important responsibility in monitoring the ongoing safety of medicines and are widely accessible to do it. This study aims to investigate the knowledge, perceptions and practice of Pharmacovigilance amongst community pharmacists in Lagos State, South West Nigeria

Medication errors among health professionals in Nigeria: A national survey

BACKGROUND Medication errors are preventable causes of patient harm with significant contributions to adverse drug events but they remain understudied in Nigeria. OBJECTIVES To estimate the prevalence of self-reported medication errors among health professionals and examine their knowledge of medication errors with the hope of identifying appropriate measures to promote medication safety. METHODS A cross sectional survey among doctors, pharmacists and nurses in 10 tertiary hospitals. Information was obtained using a self-administered structured questionnaire. Correct responses evaluating the knowledge of prescription, dispensing and administration errors were scored one mark each and the composite scores computed. Appropriate statistics were applied to summarize and establish the relationship between variables at 5% level of significance using SPSS 17.0. RESULTS A total of 2,386 professionals participated in the study (46.3% nurses, 44.9% doctors, 8.8% pharmacists).The prevalence of self-reported medication errors was 47%.The professional groups differ in their knowledge of all the aspects of medication errors with professional cadres influencing knowledge.Overwork was the most reason for being error prone (59.2%) and only 35.5% had ever reported medication error. 33.4% did not think reporting was necessary. CONCLUSIONS The prevalence of medication errors is high among health care professionals in Nigeria. Knowledge gaps and practice deficiencies were identified requiring interventions.

Potential of novel phytoecdysteroids isolated from Vitex doniana in the treatment depression: Involvement of monoaminergic systems

Vitex doniana Sweet (Verbanaceae) is used in traditional African medicine for the treatment of neurological disorders including depression. In our previous studies, three new phytoecdysteroids were isolated from methanol stem bark extract of V. doniana (VD) (11β-hydroxy-20-deoxyshidasterone, 21-hydroxyshidasterone, and 2,3-acetonide-24-hydroxyecdysone) along with known ecdysteroids. This study was designed to investigate antidepressant-like effect of VD and the isolated phytoecdysteroids in behavioral models of despair, forced-swim test (FST) and tail-suspension test (TST) in mice. VD (100 and 200mg/kg, p.o.) treatment reduced (P<0.05) the duration of immobility in both tests without affecting the locomotor activity and exploratory behavior as observed in the open field test. Similarly, 21-hydroxyshidasterone, 11β-hydroxy-20-deoxyshidasterone, ajugasterone and 24-hydroxyecdysone acute oral treatments significantly reduced immobility time with peak effect at 10mg/kg, which was similar to the effect of conventional antidepressants (imipramine and fluoxetine) in the FST. Conversely, pretreatment of mice with yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist), ketanserin (5mg/kg, i.p., 5-HT2A/2C receptor antagonist) or sulpiride (dopamine D2 receptor antagonist) prevented the antidepressant-like effect of 21-hydroxyshidasterone while the effects of 11β-hydroxy-20-deoxyshidasterone and 24-hydroxyecdysone were blocked by yohimbine or ketanserin in the FST. Moreover, the anti-immobility effect elicited by ajugasterone was prevented by prazosin (62.5μg/kg, i.p., α1-adrenoceptor antagonist) pretreatment. Our findings demonstrated that V. doniana and its phytoecdysteroids constituents elicited antidepressant-like effect in behavioral paradigm of despair. Furthermore, 21-hydroxyshidasterone produces its antidepressant-like effect through interaction with α2-adrenoceptor, 5-HT2A/2C receptor and dopamine D2-receptors but 11β-hydroxy-20-deoxyshidasterone and 24-hydroxyecdysone effects depend on interaction with α2-adrenoceptor and 5-HT2A/2C receptors while ajugasterone produces its action through interaction with post-synaptic α1-adrenoceptors. Thus, phytoecdysteroids could play a pivotal role in the treatment of major depression.

Evaluation of acute toxicity in mice and subchronic toxicity of hydroethanolic extract of Parinari curatellifolia Planch (Chrysobalanaceae) seeds in rats

Parinari curatellifolia seeds are ethnobotanically used in the treatment of diabetes and other diseases. The seed drug preparations are administered over a long period of time in the treatment of certain disease conditions. The aim of this study was to evaluate the safety of the seed extract through acute toxicity study. Also subchronic toxicity in the animals was carried out by assessing the effects on biochemical parameters, body weight and liver, heart and renal organs following oral administration of aqueous ethanolic extract of the seeds. Toxicity of the extract was evaluated in Swiss albino mice by feeding the animals with graded doses of the extract between 1.0 to 20.0 g/kg body weight orally and observed continuously for the first 4 h and every hourly for the next 24 h, then 6 hourly for 48 h (72 h, acute toxicity). Wistar rats were also fed with different extract doses for at least 30 days and the effects on biochemical parameters evaluated (subchronic toxicity model). The median acute toxicity value (LD50) of P. curatellifolia seeds extract was found to be 7.27 g/kg body weight. The extract reduced plasma glucose and low density lipoprotein (LDL)-cholesterol levels, but increased high density lipoprotein (HDL)–cholesterol in the treated groups compared to the control. A significant increase in the body weight was observed in all the groups treated with the extract. Aspartate aminotransferases (AST), creatinine and phosphorus levels were significantly increased only in the group treated with highest dose of the extract while significant decrease in alanine aminotransferases (ALT) level was observed in all groups. The LD50 value indicated the drug to be quite safe in one dose treatment. The study also showed that the extract had good hypoglycemic effects and good reducing effects on the cardiovascular risk factors but indicated that high dose of the extract on a long term use can cause liver and kidney problems.

Effect of vitamin A and vitamin C supplementation on oxidative stress in HIV and HIV-TB co-infection at Lagos University Teaching Hospital (LUTH) Nigeria

BACKGROUND HIV and TB infections are both associated with elevated oxidative stress parameters. Anti-oxidant supplementation may offer beneficial effects in positively modulating oxidative stress parameters in HIV and HIV-TB infected patients. We investigated the effects of vitamin A and C supplementation on oxidative stress in HIV infected and HIV-TB co-infected subjects. METHODS 40 HIV/TB co-infected and 50 HIV mono-infected patients were divided into 2 equal groups. Participants provided demographic information and blood was collected to determine oxidative stress parameters before and after vitamin A (5000 IU) and C (2600 mg) supplementation for 1 month. RESULTS There was a significantly (p < 0.05) higher level of Malondialdehyde (MDA) at baseline for HIV infected subjects compared with HIV-TB co-infected subjects. There was a significantly (p < 0.05) lower level of MDA and higher level of Catalase (CAT) in subjects administered supplementation compared to subjects without supplementation for the HIV infected group. There was a significantly lower level of Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and higher level of MDA after one month of supplementation compared with baseline levels for HIV/TB co infected subjects. A similar result was also obtained for the HIV mono-infected groups which had a significantly lower level of SOD, MDA and CAT compared to the baseline. There was a significantly lower level of GSH and SOD, and higher level of MDA after supplementation compared with the baseline for HIV/TB co-infected subjects. Comparing the indices at baseline and post no-supplementation in HIV/TB co-infection showed no significant differences in the oxidative stress parameters. CONCLUSION HIV/TB co-infection and HIV mono-infection seems to diminish the capacity of the anti-oxidant system to control oxidative stress, however exogenous anti-oxidant supplementation appears not to have beneficial roles in positively modulating the associated oxidative stress.

Antimalaria Action of Antiretroviral Drugs on Plasmodium berghei in Mice

Malaria parasitemia enhances replication of human immunodeficiency virus. Antiretroviral drugs that possess antiplasmodial activity may reverse such an effect. Activity of the antiretroviral drugs lamivudine (L), zidovudine (Z), nevirapine (N), and stavudine (S) against Plasmodium berghei inoculated into 70 adult albino mice was investigated. Eight groups of five animals each were treated with different drugs as either curative or prophylactic regimens. These regimens were also given to four groups as L/Z/N or L/S/N. Z therapy alone and L/Z/N eliminated malaria parasites as follows: curative and prophylactic Z groups, mean ± SEM = 62,132.87 ± 22,816.1 parasites/μL and 62,474.85 ± 14,639.1 parasites/μL, respectively on day 4 and 0 parasites/μL on day 26; curative L/Z/N group, 31,583.53 ± 6,361.67 parasites/μL, and 0 parasites/μL (days 4 and 18, respectively); prophylactic L/Z/N group, 41,138.1 ± 3,528.03 parasites/μL, and 0 parasites/μL (days 4, and 20 respectively). Peters four-day suppressive values were 67-82.2%. Zidovudine or L/Z/N therapy may modify the epidemiology of malaria and therefore the pandemic of human immunodeficiency virus infection.

How do we prevent the burden of extremely harmful and clinically nonbeneficial drug–drug interactions among chronic kidney disease patients?

The chronic intake of different medications by chronic kidney disease (CKD) patients predisposes them to extremely harmful and clinically nonbeneficial drug–drug interactions (DDIs) which can ultimately lead to increase in morbidity, mortality, healthcare cost, and frequency and length of hospitalization. This produces a negative deteriorating and counter-efficient outcome on the health, quality of life and treatment response of these patients. This was an 18-month prospective descriptive study that reviewed the medical case records of consented adult CKD patients attending the Nephrology medical outpatient clinic of a Nigerian Tertiary Healthcare Centre from January 2015 to June 2016. The Medscape drug reference database was used to evaluate patients’ medications for extremely harmful, clinically nonbeneficial DDIs. This study involved 123 consented adult CKD patients comprising of 82 (66.67%) males and 41 (33.33%) females with a mean age of 53.81 ± 16.03 years. In this study, the prevalence of extremely harmful, clinically nonbeneficial DDIs (type D or type X interaction categories only) was 24.4%, while the overall prevalence for all the observed DDIs was 95.9%. The most frequent extremely harmful, clinically nonbeneficial DDIs in this study was between α-methyldopa and metoclopramide: 16 (0.9%) interactions in eight (6.5%) patients. Furthermore, α-methyldopa decreases the antiemetic effects of metoclopramide by pharmacodynamics antagonism at the chemoreceptor trigger zone site D2-receptors (type X; pharmacodynamics). In addition, metoclopramide decreases the level of α-methyldopa by inhibition of gastrointestinal tract (GIT) absorption, as this applies to only oral formulations of both agents (type D; pharmacokinetic). The occurrence and burden of extremely harmful, clinically nonbeneficial DDIs is significantly high among these CKD patients. There is also a critical need to minimize the number of prescribed medications for these patients in order to optimize their care.

The approach of general practitioners in Lagos to the detection and evaluation of hypertension

IntroductionHypertension (HTN) control is a major public health and clinical challenge. A number of guidelines exist globally to assist in tackling this challenge. The aim of this study was to determine conformity of the HTN detection and evaluation practices of a sample of Lagos-based general practitioners (GPs) to international guidelines.MethodsSelf-administered structured questionnaires were used to collect data from a cohort of GPs attending continuing medical education programs in Lagos.ResultsOut of the 460 GPs that were approached, 435 agreed to participate in the study, with questionnaires from 403 GPs analyzed. The average age and number of years post-registration of the GPs were 40.0 ± 11.3 years and 14.3 ± 11.1 years, respectively. Two thirds (n = 269) were in private practice. Their daily average total and HTN patients’ loads were 17.4 ± 14.3 and 4.4 ± 3.5, respectively. Awareness of HTN guidelines was 46.7% (n = 188), while 18.1% (n = 73) was able to name one or more HTN guidelines. The approaches of these GPs to the detection and evaluation of HTN and their relationships to the GPs’ experience were heterogeneous.DiscussionThe approach of the GPs to detection and evaluation of HTN though heterogeneous is unsatisfactory and may partly contribute to poor HTN control in Nigeria. Strengthening the capacity of GPs in this regard through continuous medical education may greatly improve HTN control.

Role for monoaminergic systems in the antidepressant and anxiolytic properties of the hydroethanolic leaf extract from Adenia cissampeloides.

Abstract Background: Adenia cissampeloides (Planch ex. Hook) Harms (Passifloraceae) leaf infusion is used in traditional African medicine as a stimulant to treat depression and insanity. Thus, this study investigates antidepressant and anxiolytic activities of the hydroethanol leaf extract of Adenia cissampeloides (ACE) in mice. Methods: ACE (50–200 mg/kg, p.o.) was administered to mice 1 h before behavioral studies; the forced swimming test (FST), tail suspension test (TST), elevated-plus maze test (EPM) hole-board test (HBT) and open field test (OFT). In addition, the probable mechanisms of antidepressant- and anxiolytic-like actions of ACE were also investigated. Results: ACE (100 and 200 mg/kg) produced significant (p<0.01) reduction in immobility, along with a significant increase in swimming activity (75.20%) and climbing (190.00%), respectively, similar to anti-immobility effect of imipramine in the FST. Also, in TST, ACE (100 and 200 mg/kg) treatment significantly (p<0.01) reduced the immobility time by 35.60%, and 35.27%, respectively, which was similar to anti-immobility effect of fluoxetine (32.50%). However, the antidepressant-like effect produced by ACE was prevented (p<0.01) by yohimbine (α2-adrenoceptor antagonist), or sulpiride (dopamine D2 receptor antagonist) pretreatment. ACE (50 and 100 mg/kg) treatment (p<0.01) increased number (41.67%) and duration of head-dips (52.27%) in HBT. Similarly, ACE (50–200 mg/kg) increased duration of open arm entries (p<0.001) in EPM. However, this effect was reversed (p<0.001) by pretreatment of mice with cyproheptadine (5-HT2 receptor antagonist) (60.87%). Conclusions: Findings from these studies revealed antidepressant-like effect of ACE mediated through interaction with dopamine D2- receptor or α2-adrenoceptor. Also an anxiolytic-like effect through interaction with 5-HT2 receptors.

Potential drug–drug interactions in HIV-infected children on antiretroviral therapy in Lagos, Nigeria

Background Multi-therapy is common in HIV-infected children, and the risk for clinically significant drug interactions (CSDIs) is high. We investigated the prevalence of CSDIs between antiretroviral (ARV) and co-prescribed drugs for children attending a large HIV clinic in Lagos, Nigeria. Methods The case files of pediatric patients receiving treatment at the HIV clinic of the Lagos University Teaching Hospital (LUTH), Idi-Araba, between January 2005 and December 2010 were reviewed. The ARV and co-prescribed drug pairs were evaluated for potential interactions using the Liverpool HIV Pharmacology Group website. The potential interactions were rated as A (no known interaction), B (minor/no action needed), C (moderate/monitor therapy), D (major/therapy modification), and X (contraindicated/avoid combination). Results Of the 310 cases reviewed, 208 (67.1%) patients were at risk of CSDIs. Artemisinin-based combination therapy was prescribed for over one-half of the patients, accounting for 40% of the CSDIs. Excluding this drug class, the prevalence of CSDIs reduced from 67.1% to 18.7% in 58 patients. Most of the CSDIs (579; 97.2%) were moderately significant and frequently involved nevirapine and fluconazole (58; 9.7%), zidovudine and fluconazole (55; 9.2%), zidovudine and rifampicin (35; 5.9%), and nevirapine and prednisolone (31; 5.2%). Age (P=0.392), sex (P=0.783), and moderate (P=0.632) or severe (P=0.755) malnutrition were not associated with risk for CSDIs. Conclusion There is a tendency for CSDIs between ARV and co-prescribed drugs among the group of children evaluated in this study. Measures are necessary to prevent important drug interactions and to manage those that are unavoidable.